Transcatheter Mitral Valve Replacement for Mitral Valve Regurgitation

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: HighLife SAS

Must be taking: GDMT

Disqualifiers: Mitral stenosis, Rheumatic valve disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the HighLife Transcatheter Mitral Valve Replacement System. It targets individuals with severe mitral valve regurgitation, a condition where the heart's mitral valve fails to close properly, causing blood to flow backward. The trial aims to determine if this treatment is safe and effective for those unable to undergo surgery due to other health risks. Suitable candidates have severe mitral regurgitation and have been advised that surgery poses too high a risk. As an unphased trial, it provides patients the chance to access a potentially life-changing treatment before it becomes widely available.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must be on maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months before participating.

What prior data suggests that the HighLife Transcatheter Mitral Valve Replacement System is safe for patients with mitral valve regurgitation?

Research has shown that the HighLife Transcatheter Mitral Valve Replacement System has been tested with promising results. In one study, doctors successfully placed the device in 90% of patients. After 30 days, 83% of these patients experienced positive outcomes with the device.

However, some risks exist. Major bleeding and blood vessel problems occurred in 13% of patients, and 17% of patients passed away. Despite these risks, the system demonstrates a high success rate in terms of placement and excellent valve function after one year.

These findings suggest that while the HighLife system works well for many, safety concerns remain, particularly for those who may not be ideal candidates for surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for mitral valve regurgitation, which often involve open-heart surgery or medical management, the HighLife Transcatheter Mitral Valve Replacement System is a minimally invasive alternative. This system features a transcatheter mitral valve and a unique sub-annular implant, which can be delivered through the blood vessels, reducing the need for open surgery. Researchers are excited about this treatment because it offers a potential solution for patients who are at high risk for surgical complications or for whom surgery isn't an option. With its innovative delivery system, the HighLife TMVR could significantly reduce recovery times and improve patient outcomes.

What evidence suggests that the HighLife Transcatheter Mitral Valve Replacement System is effective for mitral regurgitation?

Research has shown that the HighLife Transcatheter Mitral Valve Replacement (TMVR) System, which participants in this trial will receive, could be a promising treatment for severe mitral regurgitation, a condition where the heart's mitral valve doesn't close properly. Early results indicated that the device was successfully implanted in 90% of patients. In these cases, the valve functioned well, with an 83% success rate after 30 days. However, some complications occurred, including a 13% rate of major bleeding and a 17% death rate. Despite these risks, the system may offer a potential option for high-risk patients who cannot undergo traditional surgery. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe mitral valve regurgitation who are at high risk for surgery. Candidates must have been on medical therapy for a month, be in NYHA Functional Class II-IV, and meet specific anatomical criteria. Exclusions include recent stroke/TIA, severe carotid stenosis, pregnancy, inability to follow up or take blood thinners, recent pacemaker implantation, active infections or ulcers.

Inclusion Criteria

I am willing to join the study and have signed the consent form.

You are at a high risk for open-heart surgery based on evaluations from a team of heart doctors, considering other health problems, weakness, and difficulty performing daily activities.

I have some limitations on physical activity due to heart problems.

Exclusion Criteria

I have not had an active ulcer or GI bleeding in the last 3 months.

My doctor expects I have less than 12 months to live due to a non-heart related condition.

I cannot tolerate blood thinners or medications that prevent blood clots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo the trans-septal mitral valve replacement procedure using the HighLife TSMVR system

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and performance of the HighLife TSMVR system at 30 days post-procedure

4 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and performance of the HighLife TSMVR system

6 months

What Are the Treatments Tested in This Trial?

Interventions

• HighLife Transcatheter Mitral Valve Replacement System

Trial Overview

The study tests the HighLife Transcatheter Mitral Valve Replacement System's safety and performance in patients with significant heart valve leakage who can't undergo standard surgery. It involves placing a new valve via catheter without open-heart surgery.

How Is the Trial Designed?

Group I: Transcatheter Mitral Valve Replacement Experimental Treatment 1 Intervention

HighLife TMVR System is a novel and innovative approach developed as an alternative treatment for severe MR when medical treatment is maximal and surgical interventions not possible or at high risk. The HighLife TMVR system is composed of a Transcatheter Mitral Valve (TMV), a sub-annular implant (SAI), and their delivery systems and loading tools.

HighLife Transcatheter Mitral Valve Replacement System is already approved in European Union, United States for the following indications:

Approved in European Union as HighLife TSMVR for:

• Moderate-severe and severe mitral regurgitation in patients at high risk for surgical treatment

Approved in United States as HighLife TSMVR for:

• Moderate-severe and severe mitral regurgitation in patients at high risk for surgical treatment (under clinical investigation)

Who Is Running the Clinical Trial?

HighLife SAS

Lead Sponsor

Trials

5

Recruited

430+

Published Research Related to This Trial

Transcatheter mitral valve replacement offers a promising alternative for high-risk patients with mitral regurgitation who are not suitable for traditional surgical valve replacement due to factors like advanced age or severe left ventricular dysfunction.

Recent advancements in transcatheter valve technology and data on their durability suggest that these devices could eventually be used in lower-risk populations, expanding treatment options for mitral valve disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spectrum of transcatheter mitral valve replacement devices. Dudiy, Y., Brownlee, A., Ruiz, CE.[2016]

In a study of 400 high-risk patients with symptomatic mitral regurgitation undergoing transcatheter mitral valve replacement (TMVR), the procedure achieved a technical success rate of 95.2% and resulted in significant improvements in heart function over 2 years.

Despite the high success rate, the 2-year all-cause mortality rate was 38.1%, with chronic obstructive pulmonary disease and other health factors identified as predictors of mortality, highlighting the need for careful patient selection and management to enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of transcatheter mitral valve replacement: two-year results of the CHOICE-MI Registry. Ludwig, S., Perrin, N., Coisne, A., et al.[2023]

A novel technique for transcatheter mitral valve replacement (TMVR) was successfully performed on three high-risk patients, involving the perforation and ballooning of the anterior mitral leaflet to prevent left ventricular outflow tract (LVOT) obstruction, achieving a 100% procedural success rate.

Intraoperative assessments showed no significant LVOT obstruction, indicating that this method may enhance the safety and efficacy of TMVR in patients who are not candidates for traditional surgical approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction (BATMAN): A novel technique for patients undergoing transcatheter mitral valve replacement. Helmy, T., Hui, DS., Smart, S., et al.[2020]

In a study of 25 patients with severe mitral regurgitation, 11 were successfully screened for transcatheter mitral valve replacement, demonstrating that this procedure can be a safe and effective treatment for well-selected patients, with no mortality reported in those treated with the Tendyne device.

Among the 14 patients who failed screening, alternative treatments such as the MitraClip procedure and open surgical repairs were successfully performed, indicating that there are viable options for patients who do not qualify for transcatheter replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-centre first experience with transapical transcatheter mitral valve replacement with an apical tether: factors influencing screening outcomes. Dahle, G., Helle-Valle, T., Beitnes, JO., et al.[2020]

Repeat transcatheter mitral valve replacement (rTMVR) can lead to shorter ICU and hospital stays compared to repeat surgical mitral valve replacement (rSMVR), making it a potentially safer option for high-risk patients.

While rTMVR has a comparable mortality rate to rSMVR, it is associated with a higher risk of reoperations, indicating that careful patient selection is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Outcomes After Transcatheter Versus Surgical Repeat Mitral Valve Replacement. Arafat, AA., Zahra, AI., Alhossan, A., et al.[2023]

The novel Cephea transcatheter mitral valve replacement system demonstrated excellent biological performance and safety in a preclinical model, with all 10 sheep surviving the study without complications and showing no signs of thrombosis or excessive calcification.

The transseptal delivery method was feasible and effective in pigs, with stable valve positioning and good hemodynamic profiles confirmed through echocardiography and autopsy, suggesting potential for future human applications in treating severe mitral regurgitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Evaluation of a Novel Percutaneous Transseptal Catheter-Based Mitral Valve Replacement Technology. Vahl, TP., Grogan, A., Cheng, Y., et al.[2020]

Transcatheter mitral valve replacement (TMVR) shows high procedural success in patients with severe mitral regurgitation who are at high surgical risk, indicating it could be a valuable alternative to traditional surgery.

Despite its promise, TMVR faces challenges such as potential left ventricular outflow tract obstruction and thrombotic risks, highlighting the need for further studies on long-term outcomes and optimal anticoagulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Catheter-based Mitral Valve Replacement. Rawish, E., Schmidt, T., Eitel, I., et al.[2021]

Transcatheter mitral valve replacement (TMVR) using a new self-expanding valve was successfully performed in 50 high-risk patients with symptomatic severe mitral regurgitation, achieving a high device implant success rate of 96%.

At a median follow-up of 173 days, 79% of patients showed significant improvement in their symptoms, with mild or no residual mitral regurgitation confirmed by echocardiography, indicating the procedure's efficacy in enhancing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience With New Transcatheter Mitral Valve Replacement. Bapat, V., Rajagopal, V., Meduri, C., et al.[2022]

In a study of the first 100 patients undergoing transcatheter mitral valve replacement (TMVR), the procedure demonstrated a high technical success rate of 96% and an acceptable safety profile, with no intraprocedural deaths and only one major complication.

At one year post-procedure, 72.4% of patients were alive, with significant improvements in heart function and quality of life, as evidenced by 88.5% of survivors achieving New York Heart Association class I/II status and notable enhancements in walking distance and cardiomyopathy questionnaire scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Feasibility Study of a New Transcatheter Mitral Prosthesis: The First 100 Patients. Sorajja, P., Moat, N., Badhwar, V., et al.[2020]

Transcatheter mitral valve replacement (TMVR) is a new treatment for severe mitral regurgitation, but it currently has a high 30-day mortality rate exceeding 30%, indicating significant risks associated with the procedure.

Despite its challenges, TMVR has shown promise in treating patients with degenerative mitral stenosis and failed mitral repairs, leading to ongoing multicenter registries aimed at improving device design and understanding the procedure's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves. Sarkar, K., Reardon, MJ., Little, SH., et al.[2019]

The Mi-thos TMVR system was successfully implanted in all 10 high-risk patients with severe mitral regurgitation, demonstrating a 100% intraoperative success rate without any periprocedural mortality or major complications during the 30-day follow-up.

All patients showed no or trace mitral regurgitation after the procedure, indicating effective valve function, with a median mitral valve gradient of 2.0 mmHg, suggesting that the Mi-thos TMVR system is a safe and feasible option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience. Yang, Y., Chen, J., Dong, L., et al.[2023]

The study evaluated the feasibility and safety of transseptal transcatheter mitral valve replacement (TSMVR) in four patients with severe mitral regurgitation, achieving technical success with no residual regurgitation or major complications immediately after the procedure.

While the procedure was deemed relatively safe, three major cardiovascular events occurred within 30 days, indicating the need for careful monitoring and further research on long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and safety of transseptal transcatheter mitral valve replacement for severe mitral regurgitation]. Chen, F., Zhao, ZG., Yao, YJ., et al.[2023]

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The HighLife TSMVR Feasibility Study

The 1-year results from the HighLife TSMVR feasibility study demonstrate a high technical success rate, excellent valve function, no left ventricular outflow ...